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PXD033447 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning
DescriptionPrecise vascular patterning is critical for normal growth and development. The ERG transcription factor drives Delta like ligand 4 (DLL4)/Notch signalling and is thought to act as pivotal regulators of endothelial cell (EC) dynamics and developmental angiogenesis. However, molecular regulation of ERG activity remains obscure. Using a series of EC specific Focal Adhesion Kinase (FAK)-knockout (KO) and point-mutant FAK-knockin mice, we show that loss of ECFAK, its kinase activity or phosphorylation at FAK-Y397, but not FAK-Y861, reduces ERG and DLL4 expression levels together with concomitant aberrations in vascular patterning. Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins identified that endothelial nuclear-FAK interacts with the de-ubiquitinase USP9x and the ubiquitin ligase TRIM25 enzymes. Further in silico analysis corroborates that ERG interacts with USP9x and TRIM25. Moreover, ERG levels are reduced in FAKKO ECs via a ubiquitin-mediated post-translational modification programme involving USP9x and TRIM25. Re-expression of ERG in vivo and in vitro rescues the aberrant vessel sprouting defects observed in the absence of ECFAK. Our findings identify ECFAK as a regulator of retinal vascular patterning by controlling ERG protein degradation via TRIM25/USP9x.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlex von kriegsheim
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-25 04:09:16ID requested
12022-07-05 03:21:18announced
Publication List
D'Amico G, Fernandez I, G, รณ, mez-Escudero J, Kim H, Maniati E, Azman MS, Mardakheh FK, Serrels B, Serrels A, Parsons M, Squire A, Birdsey GM, Randi AM, Bolado-Carrancio A, Gangeswaran R, Reynolds LE, Bodrug N, Wang Y, Wang J, Meier P, Hodivala-Dilke KM, ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning. Development, 149(13):(2022) [pubmed]
Keyword List
submitter keyword: RIME, HUVEC, FAK
Contact List
Alex von Kriegsheim
contact affiliationUniversity of Edinburgh
contact emailavonkri@ed.ac.uk
lab head
Alex von kriegsheim
contact affiliationUniversity of Edinburgh
contact emailalex.vonkriegsheim@ucd.ie
dataset submitter
Full Dataset Link List
Dataset FTP location
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